The direction of net fluid transport in the gut is determined by the algebraic sum of Na+ absorption and Cl- secretion. Na+ absorption by small intestinal villous cells and colonic surface cells is controlled primarily by electrically neutral (NaCl) and electrogenic (Na+-glucose, Na+-amino acid, amiloride-insensitive, and amiloride-sensitive Na+ conductance) entry processes in the apical membrane. Neutral NaCl entry appears to be the result of parallel Na+:H- and Cl-:HCO3- exchangers operating at equal stoichiometry. Uncoupled exchangers operating at different stoichiometry may result in net HCO3- absorption (jejunum), net HCO3- secretion (ileum and proximal colon) or HCO3-:Cl- exchange (distal colon). Increases in intracellular cyclic nucleotides and/or ionized Ca2+ inhibit NaCl entry and, in vivo, promote HCO3- and Cl- secretion. Cl- secretion by crypt cells is the result of cyclic nucleotide-mediated or Ca2+-mediated Cl- conductance channels in the apical membrane which allow Cl- to exit down an electrochemical gradient created by a basolateral NaKCl2 entry process. Cyclic nucleotides may act via specific A and G protein kinases. They also release Ca2+ from intracellular stores and thus could alter transport via Ca2+ (and calmodulin)-activated kinases. Ca2+-dependent secretory agents initiate phospholipid hydrolysis and stimulate secretion via the resulting hydrolytic products: arachidonic acid metabolites when bradykinin is the stimulus or diacylglycerol and/or inositol trisphosphate when acetylcholine is the stimulus. The arachidonic acid metabolites may then stimulate cyclic nucleotide production, while diacylglycerol activates a specific Ca2+/phospholipid-dependent protein kinase (C kinase), and inositol trisphosphate releases Ca2+ from the endoplasmic reticulum. The interrelationships between these intracellular messengers and their exact modes of action remain to be clarified.
|Original language||English (US)|
|Number of pages||20|
|Journal||Ciba Foundation symposium|
|State||Published - 1985|
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